tbuckley/cabot-search huggingface dataset:
Response: Re: Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability
Authors: H. B. Carter, L. Ferrucci, A. Kettermann, P. Landis, J. Wright, J. I. Epstein, B. J. Trock, E. J. Metter
Journal: JNCI Journal of the National Cancer Institute (2007)
A phase II study of lenvatinib in patients with progressive, recurrent/metastatic adenoid cystic carcinoma.
Authors: Vatche Tchekmedyian, Eric Jeffrey Sherman, Lara Dunn, Crystal Tran, Nora Katabi, Ai Ni, Sofia Haque, David G. Pfister, Alan Loh Ho
Journal: Journal of Clinical Oncology (2018)

6022 Background: Recurrent/metastatic adenoid cystic carcinoma (R/M ACC) is a malignant neoplasm of salivary gland origin with no standard treatment. The majority of ACCs are characterized by MYB over-expression which correlates to upregulation of several genes, including lenvatinib-relevant targets such as vascular endothelial growth factor A, the receptor tyrosine kinase KIT and fibroblast growth factor 2. We hypothesize that the multi-tyrosine kinase inhibitor (TKI) lenvatinib could be an effective therapy for R/M ACC. Methods: In a minimax two stage phase II study, patients with R/M ACC were treated with lenvatinib 24mg orally once daily. The protocol required new or progressive lesions radiographically and/or new or worsening disease related symptoms within 6 months of enrollment. The primary endpoint was overall response rate (ORR) (ORR= complete response (CR)+partial response (PR)) as documented by RECIST v1.1. The objective was to detect a difference in ORR of 5% versus 20% (with a one-sided type I error of 10% and power of 90%). ≥4 responses out of 32 patients was the pre-specified target for a positive study. Results: From 6/2/2016-5/22/2017, 33 patients were enrolled and 32 were evaluable for the primary endpoint (1 screen fail). The ORR was 15.6%. For best overall response (BOR), 5 patients (15.6%) had confirmed PR, 24 (75%) had stable disease (including 16 (50%) with tumor regression), and 1 (3.1%) had progression of disease (POD); 2 (6.3%) were removed prior to re-imaging. Five patients remain on therapy (range 11.0-19.9m). Reasons for discontinuation included POD (7), withdrawal of consent (9), physician discretion (6), and protocol-mandated removal for toxicity (5: myocardial infarction, posterior reversible encephalopathy syndrome, proteinuria, oral cavity fistula, and intracranial hemorrhage). 20 patients underwent at least one dose reduction.Median progression free survival (PFS) was 16.4 months (95% CI 7.2-not reached). Conclusions: The trial reached its primary endpoint, demonstrating impressive efficacy with the highest ORR and longest PFS of any phase II multi-TKI ACC study published in the literature to date. Clinical trial information: NCT02780310.
Carotene Absorption
Authors: Gerald R. Onstad
Journal: JAMA (1972)

Serum carotene levels before and after oral administration of carotene and quantitative fecal fat excretion were measured in 158 patients. Low levels of serum carotene did not reliably select the patient with steatorrhea since values less than 70μg/100 ml were associated with normal fecal fat excretion in 30%. Values greater than 70μg/100 ml were associated with steatorrhea in 18%. However, after oral loading, an increase in serum carotene of 35μg/100 ml or more indicated normal fat absorption. Lesser increases were associated with steatorrhea in 80% of patients. The carotene absorption test is a simple, sensitive, and reliable screening test for steatorrhea.
PTU-064 Identification of Syne1 and Foxe1 Hypermethylation to improve Diagnosis and Management of Colerectal Neoplasia in Inflammatory Bowel Disease
Authors: C Papadia, J Louwagie, P Del Rio, M Novelli, W Atkin, C Bordi, P Bassett, A Forbes
Journal: Gut (2013)

<h3>Introduction</h3> Colitis-associated colorectal cancer (CAC) affects individuals with inflammatory bowel disease (IBD) more often and younger than cancer in the general population. Colonoscopy provides the surveillance gold standard. Changes to surveillance intervals have been made given data demonstrating that endoscopic appearance is an important predictor of future dysplasia or cancer, but adjuvant, non-invasive clinical tools are still warranted to improve surveillance outcomes and to assist in management and interpretation of dysplasia. Methylation markers may be able to do this. Material and methods <h3>Methods</h3> using reexpression profiles of colon cancer cell lines, candidate genes were identified; promising markers were tested on tissue using the Base5 methylation-profiling platform. Promoter sequences were linked with gene expression to identify epigenetically silenced genes. Marker candidates were screened using methylation specific PCR assays to assess the methylation status of 2 gene promoters (FOXE1, SYNE1) in biopsies from 93 longstanding IBD patients and 30 healthy controls. Samples included colitis-associated colorectal adenocarcinomas (n = 25); IBD-associated dysplastic lesions (n = 29); adenomas arising on a background of UC (n = 8); samples from IBD patients with no neoplasia (n = 31) and healthy controls (n = 30). <h3>Results</h3> The presence of the 2 genes significantly varied between the groups. Both were increasing likely with increased disease severity. Neither occurred in controls, whilst 60% of CAC patients had FOXE1, and 80% of CAC patients had SYNE1. <h3>Conclusion</h3> FOXE1- SYNE1 methylation markers panel demonstrated significantly increased expression in neoplastic tissue. Syne1 was highly represented in CAC. Methylation of these promoter genes might be considered a potentially useful pathology marker of neoplasia in longstanding inflammatory bowel disease. <h3>Disclosure of Interest</h3> None Declared
The elusiveness of “normal” ALT in fatty liver
Authors: Arun J Sanyal
Journal: Hepatology (2004)

We have read the comments by Dr. Ratziu and his colleagues regarding our study We agree that alanine aminotransferase (ALT) values can fluctuate, and we would like to point out that multiple sets of normal ALT values spread over a period of 6 to 24 months were available for all patients except the 16 donors for living donor transplant. A key issue is the definition of a normal ALT. The principal factors that must be considered are the methods used and the need to distinguish between statistical versus physiological normality. As discussed in our article,1. methodological differences can account for variances up to 20 IU/L when the same sample is studied using several commercially available methods. This may account for some of the variability alluded to by Dr. Ratziu. A more difficult problem is one of separating statistical from physiological "normality." The normal range for ALT, as well as most clinically used laboratory parameters, was originally established on the basis of the distribution of values in cohorts of self-reported normal individuals. These data were used clinically to define those patients who were physiologically abnormal. This, as we know, is a fallacious concept. Just as a normal creatinine does not imply a physiologically normal kidney, a normal ALT does not imply a physiologically or morphologically normal liver. We agree that the ALT values in 70% of subjects in our study fit the high-normal values for what is currently classified as a normal ALT value by the American College of Pathology Standards. We concur that they had a high probability of being physiologically abnormal. However, we would like to point out that even those who had a low-normal ALT exhibited the full spectrum of fibrosis and other features of nonalcoholic fatty liver disease as well as metabolic syndrome. We would also like to reiterate that, as suggested by Dr. Ratziu, the data were presented as internationl units per liter for the reasons outlined by Dr. Ratziu. Of the 14 subjects with low-normal ALT values (<30 IU/L) 5 had advanced fibrosis. We agree with Dr. Ratziu that our study may have been weighted toward those patients with more advanced liver fibrosis due to the retrospective nature of the study and the ascertainment bias involved in looking only at those who had a biopsy. Indeed, this was noted in the discussion section of our article and a case was made for a prospective assessment of liver histology in those with persistently normal ALT values. Finally, the issue of redefining normal ALT ranges is a complex one, and this letter is not the appropriate forum to engage in that discussion. We thank Dr. Ratziu and colleagues for their thoughtful and excellent comments and hope we have satisfied their concerns. Arun J Sanyal M.D.*, * Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA.
Excuse me!
Authors: J Granville-Chapman, R L Dunne
Journal: BMJ (2007)

Objective To test whether standard information for patients using Crunchie and Aero chocolate bars to explain bone health and risk of fracture is robust.Design Observational study.Setting Domestic kitchen in rural west Wales.Participants 10 Crunchie bars and 10 Aero bars.Main outcome measure Fracture after falls from varying heights.Results Both Crunchie and Aero bars exhibited the same T and Z scores for bone density.Crunchie bars had a lower chocolate mass index than the Aero bars.Crunchie bars are more liable to fracture.Conclusions Using Crunchie and Aero chocolate bars to explain bone structure to patients may be visually attractive but oversimplifies the situation. IntroductIonIt is important that information provided to patients as part of their treatment should be comprehensive and accurate.Within our area of practice relating to osteoporosis and fragility fracture we have noticed a tendency to compare normal, healthy bone to the finely honeycombed structure of a Crunchie (Cadbury Trebor Bassett; Bournville, Birmingham) chocolate bar and to compare abnormal, osteoporotic bone to the coarser structure of an Aero (Nestle UK; York) bar (fig 1). 1 2 Although this explanation is readily appreciated by patients and clinicians it struck us that the comparison may not be completely valid as no work has been published on the fracture potential of each bar.This might mean that with best intentions we are advising patients to aspire to a bone structure that is actually more liable to fracture.To enable us to provide accurate data to our patients we studied the fracture risk for each chocolate bar. MethodsWe randomly purchased 20 chocolate bars (10 Crunchie and 10 Aero) from a reputable high street confectioner; the number of bars was limited by research funds and our rural environment.Each bar was measured to provide information on height
Venous leg ulcers.
Journal: BMJ (1970)

With the help of expert contributors we print in this section notes on drugs in common use. Venous Leg UlcersDrugs, used locally or internally, play only a secondary part in the treatment of venous leg ulcers.Elimination of the oedema that is always present is of paramount importance.Unless this is done the ulcer will never heal, whatever drugs may be employed.Compression of the oedematous leg is therefore essential if the patient is not put to bed, which is rarely necessary or desirable.
Thirty-Fifth Annual Scientific Meeting of the American Society of Cytology
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Thirty-Fifth Annual Scientific Meeting of the American Society of Cytology Get access JNCI: Journal of the National Cancer Institute, Volume 79, Issue 2, August 1987, Page 401, https://doi.org/10.1093/jnci/79.2.401-a Published: 01 August 1987
First British heart transplant.
Journal: BMJ (1968)

PointersFinger-prints: The configuration of fingerprints can be shown to follow mathematical rules.Distinctive patterns may be associated with chromosomal anomalies (p. 321).Abnormal Chromosome Complement: Studies on 15 males with 47,XYY complement show that these patients may have behavioural problems and are often mentally subnormal but not necessarily criminal.
NIH Consensus conference. Gallstones and laparoscopic cholecystectomy
Authors: John L. Gollan, Gregory B. Bulkley, Anna Mae Diehl, Janet D. Elashoff, Michael P. Federle, Walter J. Hogan, Keith A. Kelly, David L. Massanari, Don W. Powell, Michael Sorrell, Joanne A. P. Wilson, Jeffrey S. T. Barkun, Eric B. Bass, Harvey Bernard, David L. Carr-Locke, Robert J. Fitzgibbons, Gary D. Friedman, Thomas R. Gadacz, Alan F. Hofmann, John G. Hunter, Charles K. McSherry, William C. Meyers, Frank G. Moody, David L. Nahrwold, Douglas O. Olsen, Carlos A. Pellegrini, Jacques Perissat, Joseph B. Petelin, Edward H. Phillips, Henry A. Pitt, Leslie J. Schoenfield, Nathaniel J. Soper, Steven M. Strasberg, L. William Traverso, John V. White, Karl A. Zucker, Sarah C. Kaiser, Elsa A. Bray, Bejamin T. Burton, James Everhart, John H. Ferguson, Willis R. Foster, Thomas K. Gadacz, William H. Hall, Frank A. Hamilton, Jay H. Hoofnagle, William Meyers
Journal: JAMA (1993)

APPROXIMATELY 10% to 15% of the adult population or more than 20 million people in the United States have gallstones. It is estimated that there are about 1 million newly diagnosed patients annually. The prevalence is higher in women, in association with multiple pregnancies, obesity, and rapid weight loss, as well as in older patients and in certain ethnic groups. In 1991, approximately 600 000 patients underwent cholecystectomy. As a cause of hospitalization, gallstones are the most common and most costly digestive disease, with an annual estimated overall cost of more than $5 billion. In humans, gallstones are composed principally of cholesterol, with pigment stones occurring less commonly. The formation of cholesterol stones is believed to result from the occurrence of cholesterol supersaturation, accelerated cholesterol crystal nucleation, and impaired gallbladder motility. Stones tend to grow for the first 2 to 3 years, at which point growth tends to stabilize; 85%
Hazardous Benzodiazepine Regimens in the Elderly: Effects of Half-Life, Dosage, and Duration on Risk of Hip Fracture
Authors: P. S. Wang
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: While benzodiazepine treatment is known to increase the risk of hip fracture in older populations, controversy persists over which characteristics of benzodiazepine use (e.g., elimination half-life, dosage, duration of use) are most associated with such risks. METHOD: The authors reviewed the health care utilization data of 1,222 hip fracture patients and 4,888 comparison patients frequency matched on the basis of age and gender (all were at least 65 years old). Patients were enrolled in Medicare as well as in the New Jersey Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs. Benzodiazepine use, as well as other covariates, were assessed before the index date (which was either the date of hospital admission for hip fracture surgical repair or, for the comparison subjects, a randomly assigned, frequency-matched date). RESULTS: All benzodiazepine doses ≥3 mg/day in diazepam equivalents significantly increased the adjusted risk of hip fracture by 50%. Significantly increased adjusted risks of hip fracture were seen during the initial 2 weeks of use (60% increase) and after more than 1 month of continuous use (80% increase) but not for 2–4 weeks of continuous use. Use of benzodiazepines other than long-acting agents significantly increased the risk of hip fracture by 50%. CONCLUSIONS: Even at modest doses, including some low doses currently advocated in prescribing guidelines for older patients, treatment with benzodiazepines appears to increase the risk of hip fracture. Patients appear to be particularly vulnerable immediately after initiating therapy and after more than 1 month of continuous use. Benzodiazepines with shorter half-lives appear to be no safer than longer half-life agents. Clinicians should be aware of these risks and weigh them against potential benefits when prescribing for elderly patients.
Decision Analysis-Reply
Authors: James C. Sisson
Journal: JAMA (1977)

Dr Keeler argues from the erroneous assumption that medical information can be obtained without cost. Some new knowledge may be more inexpensive than others, but none is free. As Dr Keeler points out, the information from the liver scan was not discriminating in the example of the article, but this conclusion was derived from calculations based on probabilities and outcome values pertaining to the situation. Without the calculations, either by Bayes Theorem or through decision analysis, the value or hazard of using liver scan data in making a therapeutic decision was unknown. If interpretations of liver scans are determined to be misleading and, therefore, not to be used, then a liver scan should not be performed. The scan is not costless. Physicians should think and then act, not the reverse. In complex medical problems, decision analysis will explicitly portray the possible lines of action and their consequences; thereby,
Self-regulation in hospital waiting lists
Authors: D. P Smethurst, H. C Williams
Journal: Journal of the Royal Society of Medicine (2002)

We agree with Goodfellow and Claydon (October 2001 JRSM 1 ) that the training of ®nal-year medical students and preregistration house of®cers (PRHOs) in clinical skills can be improved.Better use can be made of the induction programme for PRHOs to include training in clinical skills, particularly as there is a substantial gap between MB BS ®nal examinations and the start of the ®rst house job.This year, our induction programme at Barts and The London NHS Trust was extended to 2 days and the structure was changed.The purpose of this was threefoldÐ foremost, to enable the new PRHOs to spend more time on the wards with the outgoing house of®cers; secondly, the number of talks was reduced to those deemed essential, to prevent information overload, and a less formal approach of `stands' for other information was adopted; ®nally, the increased length of the induction allowed us to include small-group `hands-on' training in cardiopulmonary resuscitation and also training in the patient database system.We would like to expand on clinical skills for the new PRHO induction in August 2002 to include urinary catheterization, venepuncture, intravenous cannulation, arterial blood sampling and electrocardiography interpretation, using the facilities of a clinical skills laboratory.Training in needle-stick injury should be included either in induction or early in the weekly teaching sessions for PRHOs.Post-induction, we have used our Simulation Centre to train PRHOs in management of acute emergencies in respiratory medicine and cardiology, and this year two more sessions have been added in head injury and diabetic emergencies.Extending induction to more than 2 days may pose logistical dif®cultiesÐe.g.payment for PRHOs, and accommodation.Since the starting day is always a Tuesday, greater than 2 days is not feasible.
Encephalopathy Following Jejunoileostomy-Reply
Authors: William W. Faloon
Journal: JAMA (1982)

<h3>In Reply.—</h3> The suggestion by Drs Finestone and Chowdhury concerning the possible etiology of the encephalopathy that we have observed after jejunoileostomy is of interest to us. The possibility that the syndrome is related to portal vein thrombosis, however, would seem relatively remote. We can speak with some assurance about the two patients who underwent surgery to reverse the jejunoileostomy. Neither of these showed evidence of portal vein thrombosis at operation. In the other patients we can only point out that there was no evidence of collateral circulation apparent externally, and some of the physical signs usually associated with hepatic encephalopathy were not present. There was no flapping tremor, cogwheel rigidity, or sustained clonus, and the plantar reflexes were normal. In addition, the occurrence of encephalopathy was not associated with the usual precipitory factors in hepatic coma.<sup>1</sup> Perhaps more convincing is the fact that one patient (No. 7) underwent
Epidemiology of primary and secondary syphilis in the United States, 1981 through 1989
Authors: R. T. Rolfs
Journal: JAMA (1990)

Between 1981 and 1989, the incidence of primary and secondary syphilis in the United States increased 34%, from 13.7 to 18.4 cases per 100 000 persons, the highest since 1949. The populations affected most by syphilis also changed substantially. From a peak of 10.0 cases per 100 000 persons in 1982, the incidence among white men had decreased 69% by 1989 (3.2 cases per 100 000 persons). From 1982 to 1985, the incidence also decreased among black men (30%, 101.9 to 71.5 cases per 100 000) and black women (22%, 45.8 to 35.8 cases per 100 000). However, in 1986 this trend reversed, and the incidence among blacks more than doubled from 1985 to 1989 (52.6 to 121.8 cases per 100 000 persons). Racial differences in syphilis incidence increased (black-to-white incidence rate ratio in 1981 was 14.5 and in 1989 was 47.8), as did regional differences. Trends in syphilis incidence indicate changes in sexual behavior that may determine future sexual transmission of human immunodeficiency virus. Targeting resources at populations most affected by this recent epidemic is an urgent public health priority. (<i>JAMA</i>. 1990;264:1432-1437)
Corrections.
Journal: JAMA (1924)

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